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Development of artificial transcription factors for the treatment of lung and esophageal squamous cell carcinoma

Research Project

Project/Area Number 26462141
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory surgery
Research InstitutionKawasaki Medical School

Principal Investigator

Naomoto Yoshio  川崎医科大学, 医学部, 教授 (00237190)

Co-Investigator(Kenkyū-buntansha) 世良 貴史  岡山大学, 自然科学研究科, 教授 (10362443)
深澤 拓也  川崎医科大学, 医学部, 准教授 (20379845)
山辻 知樹  川崎医科大学, 医学部, 准教授 (40379730)
高岡 宗徳  川崎医科大学, 医学部, 講師 (50548568)
羽井佐 実  川崎医科大学, 医学部, 准教授 (70322229)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords肺扁平上皮癌 / Sox2 / 人口転写因子 / 肺外科 / 分子標的治療
Outline of Final Research Achievements

Sox2 was identified as a lineage specific oncogene, recurrently amplified in lung and esophageal squamous cell carcinoma (SCC). In this study, we have developed a zinc finger based artificial transcription factor (ATF) to suppress Sox2 expression in cancer cells and termed the system ATF/Sox2. A transient transfection reporter assay demonstrated that ATF/Sox2 repressed Sox2 transcriptional activity in Sox2 expressing lung and esophageal SCC cells. A recombinant adenoviral vector: Ad-ATF/Sox2 that expresses ATF/Sox2 suppressed Sox2 at the mRNA and protein levels in lung and esophageal SCC cells. Importantly, in these cells, Ad-ATF/Sox2 decreased cell proliferation and colony formation. Moreover, Ad-ATF/SOX2 significantly inhibited tumor growth in a lung SCC xenograft mouse model. These results indicate that Sox2 silencing by ATF/ Sox2 could lead to the development of effective molecular-targeted therapies for lung and esophageal SCC.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (3 results)

All 2017 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma.2016

    • Author(s)
      Fukazawa T, Guo M, Ishida N, Yamatsuji T, Takaoka M, Yokota E, Haisa M, Miyake N, Ikeda T, Okui T, Takigawa N, Maeda Y, Naomoto Y.
    • Journal Title

      Scientific Reports

      Volume: 6 Pages: 20113-20113

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 人工転写因子を用いた肺扁平上皮癌に対する新規標的療法の開発2015

    • Author(s)
      横田 悦子、深澤 拓也、山辻 知樹、高岡 宗徳、羽井佐 実、三 宅 規子、池田 智子、石田 尚正、吉田 将和、瀧川 奈義夫、世 良 貴史、猶本 良夫
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 扁平上皮癌に対する抗腫瘍剤2017

    • Inventor(s)
      猶本 良夫、深澤 拓也、世良 貴史
    • Industrial Property Rights Holder
      学校法人川崎学園
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-038047
    • Filing Date
      2017-03-01
    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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